Aims Rho-kinase activity in circulating leucocytes is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). The present study aimed to examine the long-term prognostic impact of Rho-kinase activity in circulating leucocytes in VSA patients. Methods and results We prospectively enrolled 174 consecutive patients with VSA and 50 non-VSA patients, in whom we measured Rho-kinase activity in circulating leucocytes, and they were followed for a median of 16 months. The primary endpoint was cardiac events including cardiac death, non-fatal myocardial infarction, and hospitalization for unstable angina. During the follow-up period, cardiac events occurred in 10 VSA patients (5.7%) but in none of the non-VSA patients. When we divided VSA patients into two groups by a median value of their Rho-kinase activity, the Kaplan-Meier survival analysis showed a significantly worse prognosis in VSA patients with high Rho-kinase activity compared with those with low activity or non-VSA patients (log-rank; P < 0.05, respectively). Receiver-operating characteristic curve analysis showed that Rho-kinase activity value of 1.24 was the best cut-off level to predict cardiac events in VSA patients, and multivariable analysis showed that a value above the cut-off point had the largest hazard ratio to predict poor outcome in VSA patients [hazard ratio (95% confidence interval) 11.19 (1.41-88.95); P = 0.022]. Importantly, combination of the Japanese Coronary Spasm Association risk score and Rho-kinase activity significantly improved the prognostic impact in VSA patients as compared with either alone. Conclusion Rho-kinase activity in circulating leucocytes is useful for prognostic stratification of VSA patients.

中文翻译：

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Rho激酶活性对血管痉挛性心绞痛患者循环白细胞的预后影响

目的 循环白细胞中的 Rho 激酶活性是诊断和评估血管痉挛性心绞痛 (VSA) 疾病活动性的有用生物标志物。本研究旨在检查 Rho 激酶活性对 VSA 患者循环白细胞的长期预后影响。方法和结果 我们前瞻性地纳入了 174 名连续 VSA 患者和 50 名非 VSA 患者，我们测量了循环白细胞中的 Rho 激酶活性，并对他们进行了中位随访 16 个月。主要终点是心脏事件，包括心源性死亡、非致命性心肌梗死和因不稳定心绞痛住院。在随访期间，10 名 VSA 患者 (5.7%) 发生心脏事件，但非 VSA 患者均未发生心脏事件。当我们根据 Rho 激酶活性的中值将 VSA 患者分为两组时，Kaplan-Meier 生存分析显示，与低活性或非 VSA 患者相比，具有高 Rho 激酶活性的 VSA 患者的预后显着更差（对数秩；分别为 P < 0.05）。接受者操作特征曲线分析显示，Rho-激酶活性值为1.24是预测VSA患者心脏事件的最佳截止水平，多变量分析表明，高于截止点的值具有最大的预测风险比VSA 患者预后不良 [风险比（95% 置信区间）11.19 (1.41-88.95)；P = 0.022]。重要的是，与单独使用任何一种相比，日本冠状动脉痉挛协会风险评分和 Rho 激酶活性的组合显着改善了 VSA 患者的预后影响。